Jamie has been shot. The bullet has pierced his upper arm, exited out the other side, and has come to rest about 1 inch deep in the soft tissue of his chest wall. Fortunately the bullet has avoided any bones and did not penetrate the chest wall deep enough to damage his lungs and vital organs. Jenny has cleaned the wounds as best she can and has removed the bullet but a serious infection has settled in Jamie’s arm.

The wound itself was a ragged dark hole, scabbed at the edges and faintly blue-tinged. I pressed the flesh on either side of the wound; it was red and angry-looking, and there was a considerable seepage of pus. Jamie stirred uneasily as I drew my fingertips gently but firmly down the length of the muscle.
From Voyager by Diana Gabaldon, Chapter 36

Gunshot Wounds

Gunshot wounds become infected frequently, and are considered to be contaminated wounds, which makes sense:

Soiled clothing is forced into the skin and various injured tissues during the penetration of the bullet

The trauma causes the local blood supply to the area to become disrupted, decreasing the ability of one’s immune system to defend against bacteria

Throughout history, death in combat was more often due to infection than battle injuries. Things are not looking so good for Jamie. In fact, had young Ian not rode a full day’s journey to beg Claire to return to Lallybroch to help save Jamie, the Outlander story may have had a much more rapid resolution!

Fortunately for Outlander fans, Claire had the wisdom and foresight to include a special item in the pocket of her dress in her travel back through the stones. Or perhaps it was just plain good sense, knowing she was returning to Jamie Fraser, a man whom trouble seems to find!

I laid the small, flat case on the table and flipped the latch. “I’m not going to let you die this time either,” I informed him, “greatly as I may be tempted.” I carefully extracted the roll of gray flannel and laid it on the table with a soft clicking noise. I unrolled the flannel, displaying the gleaming row of syringes, and rummaged in the box for the small bottle of penicillin tablets.
“What in God’s name are those?” Jamie asked, eyeing the syringes with interest. “They look wicked sharp.”
I didn’t answer, occupied in dissolving the penicillin tablets in the vial of sterile water. I selected a glass barrel, fitted a needle, and pressed the tip through the rubber covering the mouth of the bottle. Holding it up to the light, I pulled back slowly on the plunger, watching the thick white liquid fill the barrel, checking for bubbles. Then pulling the needle free, I depressed the plunger slightly until a drop of liquid pearled from the point and rolled slowly down the length of the spike.
“Roll onto your good side,” I said, turning to Jamie, “and pull up your shirt.”
From Voyager by Diana Gabaldon, Chapter 36

Penicillin

Penicillin was indeed a game changer for Jamie, but also for the entire world, even playing a significant role in the success of the Allies in World War II. The discovery of penicillin was a fortunate accident and starts with Scottish scientist Alexander Fleming. The story goes that upon returning to his lab in the basement of St. Mary’s Hospital in London in late September 1928 after a two week holiday, Fleming noted an interesting phenomenon in a petri dish that had been left accidentally open.

The petri dish contained Staphylococcus bacteria he had been studying, but now also contained a blue-green mold which he suspected had contaminated his petri dish from an open window. Upon closer examination, he noticed that there was a clear zone around the mold where no staph bacteria grew, as though the mold and prohibited the growth of bacteria in that area.

From Alexander Fleming’s Nobel Lecture, December 11, 1945

Fleming identified the mold as penicillium, and thus named the active substance capable of killing the surrounding bacteria penicillin. He authored a paper describing his findings but this was met with little interest. Penicillin was unstable and Fleming had difficulty producing it in any significant quantity. No further progress would be made for another decade.

In 1939, a group of scientists at Oxford including Howard Florey and Ernst Chain developed a method for purifying and producing penicillin, though the yield still remained rather low. A year later, their experiments showed that penicillin could successfully treat strep infections in mice.

Florey and Chain showed that penicillin could treat infections in human in 1941 when they treated a 48 year old policeman by the name of Albert Alexander. Mr Alexander had scratched the side of his nose while pruning roses and developed a significant infection with abscesses involving the eye, face and lungs. He was treated with penicillin and within days had a remarkable recovery. However, the supply of penicillin ran out after 5 days. His infection worsened again and he died.

By this time, the world was fully engaged in World War II. The US drug company Merck started production of penicillin and successfully treated in 1942 a patient with streptococcal septicemia – an infection of strep in the blood. However, treatment of that one patient required half of the total supply of penicillin available at the time. Work began in earnest to figure out a way to mass produce large quantities of the drug.

The US government hoped to produce enough penicillin for mass distribution to the Allied troops in Europe. In 1943, the US War Production Board took over responsibility for the increased production of penicillin with the goal to have adequate supply for the planned D-day invasion in France. Ultimately, 2.3 million doses were available in time for the invasion of Normandy in the spring of 1944. During the war effort, penicillin was limited to military use, with rare exceptions made for civilians in cases where other treatments had failed. By 1945, increased production allowed for penicillin to be available to consumers for the first time without restriction. Fleming, Florey and Chain were awarded the Nobel Prize in Physiology or Medicine in 1945.

Prior to the era of penicillin, seemingly minor infections were often life-threatening: strep throat, scarlet fever, dental infections, skin infections from simple scratches, etc. Infections like bacterial pneumonia, meningitis and endocarditis (infection of the lining of the heart and the heart valves) were often death sentences. In World War I, the death rate from bacterial pneumonia was 18%. With the availability of penicillin in World War II, that fell to less than 1%. Untreated skin infections from trauma as minor as a simple scratch carried an 11% mortality rate prior to the discovery of penicillin.

Credit: Research and Development Division, Schenley Laboratories, Inc., Lawrenceburg, Indiana

Fleming, though, foresaw the risk involved with this miracle drug and in his Nobel Lecture, provided this ominous warning:

But I would like to sound one note of warning. Penicillin is to all intents and purposes non-poisonous so there is no need to worry about giving an overdose and poisoning the patient. There may be a danger, though, in under-dosage. It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body.

-Alexander Fleming, Nobel Lecture, December 11, 1945

Antibiotic Resistance

Some suggest that we are headed to a post-antibiotic era – a time when we once again will be defenseless against seemingly simple infections. Now we have antibiotic resistant pneumonia, tuberculosis, blood infections and even gonorrhea and few, if any, effective antibiotics against them. The CDC estimates that antibiotic resistance has been responsible for over 2 million illness and 23,000 deaths each year.

Antibiotics resistance happens naturally as the bacteria adapt but we must avoid accelerating this process.

From: Center for Disease Control

As patients, we can minimize antibiotic resistance by:

Working to prevent infection with good hand washing, food hygiene and common sense, avoiding close contact with those who are ill.

Always finishing the full course of prescribed antibiotics and not taking left over antibiotics or someone else’s

It is scary to think we could be headed toward a time when we are unable to effectively fight bacterial, viral, and fungal infections. Progress continues in the development of new antibiotics, but resistance continues to develop at an alarming rate.

Fortunately, the bacteria infecting Jamie’s wound was no match for penicillin. With no prior exposure to penicillin or similar antibiotics, the bacteria would have had no resistance and would easily succumb to the novel medication. And good thing, too – without antibiotics, this wound could have been fatal for Jamie. Thus, the Outlander saga could have ended much too early, and at the hands of Laoghaire no less (as though we needed any further reason to despise her)!

Ah, the Wedding. Claire and Jamie are in no immediate threat of danger, no one is attacked, there are no poisons, no boar hunts, and aside from the superficial lacerations to the wrists of the bride and groom in the ceremony, no real risk of trauma.

The world’s oldest profession also has a long story of infectious disease to tell! We will hope that Ned came away from his night in the brothel unscathed, and perhaps he has taken some precautions.

Ned Gowan is an educated man and hopefully he made use of the protection available at the time. First documented to be used in Greece around 3000 B.C., early condoms were made of goat bladder and of linen and had not changed dramatically by the time we arrive in the 18th century, though fortunately tortoise shell and horn were no longer popular materials! Condoms of the 18th century were made of either chemically-treated linen or from animal bladder or intestine. It is unclear how widespread their use was, though they were widely sold in pubs and markets in Europe.

Syphilis and gonorrhea were the most prevalent STDs of the time. Syphilis, in particular, has severe, life-changing consequences. Known by a variety of names depending on a person’s geographic locale (everyone blames everyone else!) including “great pox,” “the disease of Naples,” “the Spanish disease,” “the French disease,” “Persian fire,” and called “grandgore” by the Scots, the first documented epidemic of syphilis is among French soldiers in 1495. Symptoms included genital sores, abscesses, and ulcers over the body and severe pain. Remedies were few and of questionable efficacy.

Syphilis is a sexually transmitted infection caused by the bacterium Treponema palladium. The disease occurs in stages and can be very disfiguring and ultimately fatal. The first sign of infection is a skin lesion called a chancre at the location exposed to the bacterium, generally on the genitals. This is classically a single skin ulceration up to 3cm in size and generally painless. Enlargement of the lymph nodes in the area is common. Without treatment, the lesion persists for 3 to 6 weeks.

Approximately 25 percent of untreated patients infected with syphilis will progress to secondary syphillis. This occurs 1-2 months after the primary infection and manifests in many ways. Generally, this involves symptoms of the skin, mucous membranes and lymph nodes including non-itchy rash to the trunk and extremities including the palms of the hands and soles of the feet. Wart-like lesions may develop on mucous membranes. All of these lesions contain the bacteria and are infectious. Fever, sore throat, weight loss, hair loss and headache also occur. Rare complications include liver involvement, kidney disease, joint inflammation, and ocular (eye) abnormalities. These symptoms will last for another 3-6 weeks.

Approximately 30-60% of those who are exposed to the wounds of someone with primary or secondary syphilis will contract the disease. The bacteria die very quickly outside of the body so transmission from objects like toilet seats, hot tubs, sharing utensils, is not thought to be possible.

Syphilis can then enter a latent phase in which there are no symptoms of the disease but blood testing will still prove infection is present.

Without treatment, one third of people infected with syphilis will develop tertiary syphilis with devastating consequences. Chronic gummas, or soft, tumor-like balls of inflammation occur in the skin, bone and liver. Syphilis can infect the heart and vascular system, leading to aortic aneurysms among other complications. Infection of the nervous system (neurosyphilis ) results in meningitis, general paresis (a progressive severe dementia along with difficulty moving the muscles of the face and limbs) and tabes dorsalis – a disease of the spinal cord leading to severe pain, impaired sensation and bladder dysfunction.

Syphilis can be transmitted from mother to child during pregnancy or childbirth and can result in stillbirth, prematurity and a number of severe and disabling symptoms including deformity of the face and teeth, bony deformity and deafness. Women who receive prenatal care are tested for spyhilis during pregnancy and treatment with antibiotics can eradicate it. Congenital syphilis, however, does remain a problem in developing countries where prenatal care is not readily available.

Portrait of Gerard de Lairesse by Rembrandt van Riin, circa 1665-67. de Lairesse had congenital syphilis leading to deformity of his face and eventual blindness. (source)

Until the 20th century, mercury was the primary treatment for syphilis – either taken orally or made into ointment and rubbed onto the skin. Mercury, unfortunately, has many toxic side effects: kidney failure, severe mouth ulcers, loss of teeth, neurologic damage and even death. The cure was deemed by some to be worse than the syphilis itself: “A night with Venus and a lifetime with mercury!”

Ultimately, it was the discovery of penicillin by Scottish scientist and Nobel laureate Alexander Fleming in 1928 that would ultimately provide the cure. In 1943, physicians at the US Marine Hospital in Staten Island, NY, proved the effectiveness of penicillin on syphilis and cured infected soldiers with intramuscular injections of penicillin.

Alexander Fleming, who is credited with discovering penicillin in 1928. (source)

The total number of cases of syphilis in the US was 575,593 in 1943, the year penicillin was proven to be effective for syphilis. This dropped to a low in 2000 of 31,618 cases. However, this has steadily been climbing since 2000 and in 2014 there were 63,450 cases! Why? This article from The Atlantic in December 2015 is a good read and discusses a few of the reasons this may be happening including aps like Tinder facilitating more casual sex, the unfamiliarity of young Americans with the risks of untreated syphilis as it isn’t in the public conscience as it had been in the past, the fear of HIV may be declining from its peak in the 1990s, leading to less use of protection.

There is no vaccine for sphilis. Prevention and early diagnosis is key, as early treatment with antibiotics can prevent the devastating effects of this disease!

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